Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer

Immunity. 2024 Mar 12;57(3):414-428. doi: 10.1016/j.immuni.2024.02.001.

Abstract

Interleukin-2 (IL-2) is a critical cytokine for T cell peripheral tolerance and immunity. Here, we review how IL-2 interaction with the high-affinity IL-2 receptor (IL-2R) supports the development and homeostasis of regulatory T cells and contributes to the differentiation of helper, cytotoxic, and memory T cells. A critical element for each T cell population is the expression of CD25 (Il2rα), which heightens the receptor affinity for IL-2. Signaling through the high-affinity IL-2R also reinvigorates CD8+ exhausted T (Tex) cells in response to checkpoint blockade. We consider the molecular underpinnings reflecting how IL-2R signaling impacts these various T cell subsets and the implications for enhancing IL-2-dependent immunotherapy of autoimmunity, other inflammatory disorders, and cancer.

Keywords: T cell exhaustion; autoimmunity; cancer immunotherapy; cytokine; cytokine signaling; effector T cells; immunotherapy; interleukin-2; interleukin-2 receptor; memory T cells; regulatory T cells.

Publication types

  • Review

MeSH terms

  • Autoimmunity
  • Humans
  • Interleukin-2* / metabolism
  • Neoplasms*
  • Receptors, Interleukin-2
  • T-Lymphocyte Subsets

Substances

  • Interleukin-2
  • Receptors, Interleukin-2